Behavioral and pharmacokinetic assessment of nicotine e-cigarette inhalation in female rats.

INTRODUCTION: Nicotine and tobacco use remain high both globally and in the USA, contributing to large healthcare expenditures. With a rise in e-cigarette use, it is important to have clinically relevant models of inhaled nicotine exposure. This study aims to extend prior preclinical nicotine inhalation animal data to females and provide both behavior and serum pharmacokinetics. METHODS: We tested two inhalation doses of nicotine (24 mg/ml and 59 mg/ml) and compared these to injected doses (0.4 mg/kg and 1 mg/kg). In addition, we assessed locomotor behavior after the same doses. Blood was collected at 10- and 120-minutes post-administration. We assessed nicotine and cotinine serum concentrations by LC-MS/MS. RESULTS: showed that while nicotine serum concentrations for the respective high and low-dose administrations were similar between both routes of administration, the route had differential effects on locomotor behavior. Inhaled nicotine showed a dose-dependent decrease in locomotor activity while injected doses showed the opposite trend. CONCLUSIONS: Our results indicate that the route of administration is an important factor when establishing preclinical models of nicotine exposures. Given that the overall use of e-cigarettes in vulnerable populations is on the rise, our study provides important behavioral and pharmacokinetic information to advance our currently limited understanding of the effects of nicotine vapor exposure. IMPLICATIONS: This study highlights behavioral differences between different routes of administration of similar doses of nicotine. Using a low and high dose of nicotine, we found that nicotine serum concentrations were similar between the different routes of administration. Our results indicate that different routes of administration have opposing effects on locomotor activity. These findings provide important implications for future behavioral models.

Calorie restriction, but not Roux-en-Y gastric bypass surgery, increases [3 H] PK11195 binding in a rat model of obesity.

Roux-en-Y gastric bypass surgery (RYGB) remains an effective weight-loss method used to treat obesity. While it is successful in combating obesity, there are many lingering questions related to the changes in the brain following RYGB surgery, one of them being its effects on neuroinflammation. While it is known that chronic high-fat diet (HFD) contributes to obesity and neuroinflammation, it remains to be understood whether bariatric surgery can ameliorate diet-induced inflammatory responses. To examine this, rats were assigned to either a normal diet (ND) or a HFD for 8 weeks. Rats fed a HFD were split into the following groups: sham surgery with ad libitum access to HFD (sham-HF); sham surgery with calorie-restricted HFD (sham-FR); RYGB surgery with ad libitum access to HFD (RYGB). Following sham or RYGB surgeries, rats were maintained on their diets for 9 weeks before being euthanized. [3 H] PK11195 autoradiography was then performed on fresh-frozen brain tissue in order to measure activated microglia. Sham-FR rats showed increased [3 H] PK11195 binding in the amygdala (63%), perirhinal (60%), and ectorhinal cortex (53%) compared with the ND rats. Obese rats who had the RYGB surgery did not show this increased inflammatory effect. Since the sham-FR and RYGB rats were fed the same amount of HFD, the surgery itself seems responsible for this attenuation in [3 H] PK11195 binding. We speculate that calorie restriction following obese conditions may be seen as a stressor and contribute to inflammation in the brain. Further research is needed to verify this mechanism.

Prenatal Effects of Nicotine on Obesity Risks: A Narrative Review.

Nicotine usage by mothers throughout pregnancy has been observed to relate to numerous deleterious effects in children, especially relating to obesity. Children who have prenatally been exposed to nicotine tend to have lower birth weights, with an elevated risk of becoming overweight throughout development and into their adolescent and adult life. There are numerous theories as to how this occurs: catch-up growth theory, thrifty phenotype theory, neurotransmitter or endocrine imbalances theory, and a more recent examination on the genetic factors relating to obesity risk. In addition to the negative effect on bodyweight and BMI, individuals with obesity may also suffer from numerous comorbidities involving metabolic disease. These may include type 1 and 2 diabetes, high cholesterol levels, and liver disease. Predisposition for obesity with nicotine usage may also be associated with genetic risk alleles for obesity, such as the DRD2 A1 variant. This is important for prenatally nicotine-exposed individuals as an opportunity to provide early prevention and intervention of obesity-related risks.

Environmental enrichment sex-dependently rescues memory impairment in FABP5 KO mice not mediated by brain-derived neurotrophic factor.

Fatty acid-binding proteins (FABPs) are intracellular carriers of bioactive lipids and play a role in the trafficking of endocannabinoids as well as polyunsaturated fatty acids. Mice lacking the FABP5 gene have memory impairments. Environmental enrichment is a potent manipulation known to rescue or improve memory performance. The extent to which the memory impairments in FABP5 knockout (KO) mice can be rescued or improved through environmental conditions remains to be understood. To address this, we raised wild type (WT) and FABP5 KO mice in either socially isolated or environmental enrichment conditions during adolescence. Once in adulthood, mice were tested for Novel Object Recognition (NOR), T-maze, and Morris Water Maze (MWM) to evaluate memory performance. Mice were then euthanized to assess hippocampal brain-derived neurotrophic factor (BDNF) concentrations. MWM results showed that male FABP5 KO mice performed worse compared to WT counterparts. Male and female mice raised in an enriched environment improved performance regardless of genotype. Results on the NOR test showed that male FABP5 KO mice displayed lower object recognition compared to WT counterparts across both environments. No differences of genotype or environment were seen in female mice. T-maze findings revealed impaired performance in socially isolated FABP5 KO mice. Adolescent environmental enrichment rescued this deficit in male, but not female, FABP5 KO mice. Lastly, environmental enrichment increased hippocampal BDNF levels in male WT mice only. Our results corroborate the previously observed role of the FABP5 gene on memory performance and identify an important interaction with the environment during adolescence.

A Woman in Her 60s With Lung Adenocarcinoma Presents With Copious Watery Sputum and Respiratory Failure.

CASE PRESENTATION: A woman in her 60s presented with 1 month of progressive dyspnea, watery rhinorrhea, and paroxysmal cough productive of clear, watery sputum. She was diagnosed with epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma at another institution 1 week prior to presentation and 3 weeks after the onset of symptoms. She was a never-smoker. She denied fevers and had completed a course of antibiotics for presumed pneumonia, without clinical improvement. She presented to the hospital due to increasing severity of her shortness of breath.